The upper respiratory tract is a primary entrance port for microorganisms entering the lungs, i.e., the lower respiratory tract, of a subject. The upper respiratory tract frequently traps these microorganisms where they may be killed before they effectively enter the lungs. However, if a microorganism is able to survive in the upper respiratory tract, the microorganism may thereafter move into the lungs. Additionally, the existence or persistence of microorganisms, such as a virus, in the upper respiratory tract may lower the effectiveness of the subject's immune system, such that the lungs become susceptible to other microorganisms that may cause secondary infections, such as bacteria that may cause bacterial pneumonia or another type of infection. Additionally, the persistence of microorganisms in the sinuses can directly cause chronic headaches, cough and nasal discharge. Therefore, targeted therapeutic or preventative treatment of the upper respiratory tract can speed the recovery from local infections and/or prevent infection in the lungs or some other part of a subject's body.
The link between an upper respiratory tract infection and infection in the lower respiratory tract is well documented. For example, the following articles, each herein incorporated by reference in their entirety, support the proposition that treating the upper respiratory tract has beneficial value to the health of the lungs and lower respiratory tract. Papadopoulos, et al., “Rhinoviruses infect the lower airways.” J. Infect. Dis. 2000; 181:1875-1884; Gern J. E., “Viral respiratory infection and the link to asthma.\,” Pediatr. Infect. Dis. J. 2004; 23 (Suppl. 1):S78-S86; Fraenkel, et al., “Lower airway inflammation during rhinovirus colds in normal and in asthmatic subjects.” Am. J. Respir. Crit. Care Med. 1995: 151:879-886; and Pizzichini, et al., “Asthma and Natural Colds. Inflammatory Indices in Induced Sputum: A Feasibility Study,” Am J. Respir. Crit. Care Med. 1998; 158:1178-84.
The focus of treatment of the upper respiratory tract is often on traditional pharmaceuticals, such as oral antibiotics. In the 1980's, it was discovered that the endothelium tissue of the human body produced nitric oxide (NO), and that NO is an endogenous vasodilator, namely, an agent that widens the internal diameter of blood vessels and is also one of the basic elements of the human body's natural defense mechanisms against microorganisms. NO is most commonly known as an environmental pollutant that is a byproduct of combustion. However, it has been discovered that inhaled NO at low concentrations can be used to treat various pulmonary diseases in patients. For example, NO has been investigated for the treatment of patients with increased pulmonary artery resistance as a result of pulmonary arterial hypertension in both adults and children and is the primary treatment for “Blue Baby” syndrome. NO has also been shown to have anti-microbial and/or microcidal activity over a broad range of microorganisms.
While NO has shown promise with respect to certain medical applications, delivery methods and devices must address problems inherent with gaseous NO delivery. First, exposure to high concentrations of NO may be toxic, especially exposure to NO in concentrations over 1000 ppm. Even lower levels of NO, however, can be harmful if the time of exposure by the lungs is relatively high. For example, the Occupational Safety and Health Administration (OSHA) has set respiratory tract exposure limits for NO in the workplace at 25 ppm time-weighted averaged for eight hours.
Another problem with the delivery of NO is that NO rapidly oxidizes in the presence of oxygen to form NO2, which is highly toxic, even at low levels. If the delivery device contains a leak, unacceptably high levels of NO2 gas can develop. In addition, to the extent that NO oxidizes to form NO2, there is less NO available for the desired therapeutic effect. The rate of oxidation of NO to NO2 is dependent on numerous factors, including the concentration of NO, the concentration of O2, and the time available for reaction. Since NO will react with the oxygen in the air to convert to NO2, it is desirable to have minimal contact between the NO gas and the outside environment.
Systems have been developed to deliver NO to the upper respiratory tract without introduction into the lungs. For example, U.S. Pat. No. 8,043,252 describes a system of delivering NO to one nostril during patient exhalation against a positive pressure to close the soft palate. However, such a system is limited as it requires patients to exhale against a pressure that may be uncomfortable for breathing or may be difficult for some patients to perform, such as patients who have had strokes or who have less control of their breathing. This can thus limit the efficacy of delivered NO in the upper respiratory tract.
Accordingly, there is a need in the art for an improved device and method for the treatment of upper respiratory tract by the administration of gaseous NO, without allowing the introduction of NO to the lungs. The present invention satisfies this need.